Agent delivery systems and devices which use an expansion means can deliver a beneficial agent to an environment of use over a period of hours, days, or months. The expansion means absorbs liquid, expands, and acts to drive out beneficial agent formulation from the interior of the device in a controlled manner.
Agent delivery devices which use an expansion means can be designed to deliver agent over a relatively short term, i.e., 20-25 days or less. Such devices generally comprise a highly permeable semipermeable membrane, together with a beneficial agent in a carrier which is liquid, relatively non-viscous, and easily extruded by the action of the expansion means. The agent delivery profile of such a short-term device is shown, for example, in FIG. 12 of U.S. Pat. No. 4,595,583, the disclosure of which is hereby incorporated by reference. As shown in U.S. Pat. No. 4,643,731, the disclosure of which is hereby incorporated by reference, instantaneous concentration of beneficial agent obtained from short-term devices can be achieved by providing a loading dose, i.e., an initial, immediate, short-term dose of beneficial agent, prior to the onset of the continuous delivery provided by the osmotic pump device.
Agent delivery devices can alternatively be designed to deliver agent over a longer term, i.e., 25-30 days or greater, and especially 60-120 days or greater. Such devices generally comprise a slowly permeable semipermeable membrane, together with a beneficial agent in a carrier which is viscous or paste-like, and extruded by the action of the expansion means over relatively longer times than shown by the short-term devices. The startup time of the device, that is, the time during which the device does not deliver beneficial agent, depends upon the rate at which the semipermeable membrane allows hydration of the system, and the rate at which the expansion means becomes hydrated sufficiently to begin extrusion of the beneficial formulation. The agent delivery curve of a device designed to deliver a given dosage for 120 days is shown, for example, in FIG. 21 of U.S. Pat. No. 4,729,793.
The teachings of the prior art pertaining to loading doses of beneficial agent regarding short-term delivery devices do not provide a solution to the problem of the startup delay in long-term devices. Due to the kinetics of the release of loading doses for short-term devices, the loading doses are active for only a short time, and do not sustain he concentration of beneficial agent during the startup period demonstrated by long-term devices. Those loading doses provided within the coating of a short-term device are not appropriate for use with long-term devices having a semipermeable membrane, as such coatings can interfere with the permeability of the semipermeable membrane, and thus interfere with the operation of the device.
Ruminant animals, including cattle, sheep, goat, deer, bison, camels and giraffe, and especially domestic animals such as cattle, sheep and goats, comprise an important group of animals that require periodic administration of medicines and nutrients. The medicines and nutrients are administered for the treatment and alleviation of various conditions, and for improved health. Ruminants have a complex stomach generally having three or four compartments. The largest of the stomach compartments is the rumen, which acts as an important location for receiving and passing medicines and nutrients into other compartments, including the abomasum and the intestine.
One method of treating ruminants requires the repeated administration of medicines and nutrient at frequent time intervals. This form of treatment is inconvenient and expensive, and does not lend itself to reliable therapy.
Prior art devices which have been designed to maintain continuous dosages of a beneficial agent for extended periods of time have the disadvantage of exhibiting a significant startup time between administration to the subject animal or human and the onset of agent delivery. Provision of effective dosages upon administration of the device has been obtained by prehydration (i.e., soaking) of the device prior to administration. For example, a prior art device which exhibits a three-week delay prior to onset of effective delivery of the desired agent can be soaked for three weeks prior to administration to the subject. Effective delivery of the desired agent thus begins upon administration.
Prehydration of a long-term device has several significant disadvantages. The soaking of a single device for a period of three weeks requires a processing step which is undesirable but which is likely to be manageable. The soaking of sufficient individual devices with which to supply an entire herd of animals can require a container the size of a swimming pool or a small lake. The active agent which is being delivered by the device is distributed into the water in which the device is soaked, and can require special treatment of the water before it can be released into ground or sewage waters. Additionally, if the device has a limited lifespan (i.e., decomposition of the semipermeable membrane, density means, or other component of the device takes place over time) the time during which the device is prehydrated may limit the effective use in the subject animal.
It is therefore an object of this invention to provide a long-term dispensing device that quickly and continuously delivers an effective amount of agent, followed by a continuous and sustained delivery of agent over a prolonged period of time.
Another object of the invention is to provide a long-term dispensing system comprising a first agent delivery means that quickly and continuously makes agent available, and a second agent delivery means that makes agent available for continuous and prolonged delivery, and thus provides a dispensing system that delivers agent quickly, continuously, and over a prolonged period of time when in operation in an environment of use.
Another object of the invention is to provide a first agent delivery means positioned within or at the surface of a long-term dispensing device comprising a second agent delivery means capable of long-term and continuous delivery of agent. The combination of first and second agent delivery means provides a device which exhibits beneficial agent rapidly delivered to the environment of use, together with continuous and prolonged delivery of agent, substantially eliminating the startup time associated with prior art devices.
Yet another object of the invention is to provide an agent delivery device comprising a means for rapid and continuous delivery of beneficial agent to the environment of use, together with a means for delivery of the beneficial agent over prolonged time which includes a semipermeable wall which surrounds and defines an internal lumen, a means in the lumen for expanding and occupying an increased volume of the lumen, a beneficial agent formulation in the lumen that provides a dispensable formulation to the environment of use, and an exit means in the device for delivery of the beneficial agent to the environment of use over time, thus substantially eliminating the startup time associated with the prior art devices. Yet another object of the invention is to provide an improvement over the prior art by making available a dispensing device possessing controlled agent availability during a period of time during which the prior art dispensing devices did not make agent available to the environment of use.
Another object of the invention is to provide an improved beneficial agent dispensing device by providing a dispensing device which is easy to manufacture, inexpensive and easy to use, makes the desired agent quickly available, and provides constant and prolonged agent availability over time.
It is another object of the invention to provide a delivery device that can remain in the rumen of a ruminant for a prolonged period of time, providing both rapid and prolonged delivery of a beneficial agent.
These and other objects, features and advantages of the invention will be more apparent to those skilled in the art from the following specification, taken in conjunction with the drawings and the accompanying claims.